Pest control composition



Patented Feb. 9, 1943 UNITED STATES PEST CONTROL OOMYOSITION JohnFi-ank Lontz, Wilmington. DcL, asaignor to E. I. du Pontde Nemours a Company, Wil mington, M, a corporation of Delaware No Drawing. Application August 5, 1941,

serial No. 405,555

.1 Claims. (oi. 167-22) v This invention relates to'pest control compositions useful as .bactericldes, fungicides, insecticides, and disinfectants.

This invention has for itsvgeneral object the provision of new and useful compositions having the power of killing or repelling economically or physiologically harmful pests, such as bacteria,

fungi, insects, and the like which prey on plant and animal matter either in its animate, inani-' mate, or fabricated state. A further object of this invention is the provision of pest control compositions, especially I bactericidal composi-' tions, having a high degree of effectiveness in the presence of tissue fluids such as blood serum.

Other objects will appear hereinafter.

These objects are accomplished by the following invention of pesticidal compositions comprising as an essential active ingredient a linear polymeric amidine salt. 'I'hese polymeric materials are defined as salts of linear polymers conm g. as integral members of the chain a multiplicityof recurring groups consisting of a trivalent nitrogen atom having one valence attached to hydrogen or to an alkyl group of 1-5 carbon atoms, and a second valence attached to 25 where A and B are divalent organic radicals having their free valences stemming from carlion and are free from groups reactive with amidine salt groups; B. and R are hydrogen or alkyl radicals of from 1-5- carbon atoms,'x is Drug Ad 4-1:

the anion of an acid, and n is the number of polymer units inthe chain. Preferably, A and B are hydrocarbon, R and R are hydrogen and X is an anion of a strong acid having an 'ionization constant of at least 10-. More preferably, X is a halogen of atomic weight between 85 and 126 and is more preferably chlorine. In a further preferred modification A- and B are hydrocarbon groups with at least 4 carbon atoms in the chain. v

The linear polymeric amidine salts can be prepared according to the processes described in Hunt and Kirby, application Serial No. 350,108.

r The salts are characterized in general by hygroscopicity and water solubility and are for the most part white powdery material's. These polymeric salts are highly efl'ective b'actericides, in many instances being effective in aqueous solutions in dilutions of 1 to 20,000 to 1 to 50,000 against Staphylococcus aureus. The linear polymeric amldine salts of this invention have a definite fungicidal effect and also an insecticidal activity,.for aample, against clothes moths and Mexican bean beetles.

The bactericidal properties of the linear polymeric amidine salts vary with the individual members of this class. Those which have been found outstanding are those prepared from aliphatic polymethylene primary diamines containing 6 or more carbons in the methylene chain, e. g., hexamethylenediamine and decamethylenedie, and the dliminoether dihydrochlorides from polymethylene dinitriles conteining 6 or more carbon atoms in the chain.

c. g., adipo' a trile and sebacodinitrile.

The polymeric salts with which this invention is concerned were tested for bactericidal action according to the standard F. D. A. (Food and tration) method. Their bacteria static activity, i. e., their eficiency for inhibiting bacterial growth, was also determined by methods well known in bacteriology.

The more detailed practice of the invention is by the folio examples, wherein parts are given by weight. They illustrate the preparation and application of certain poleric amidine salts to bactericidal, icidal and insecticidal 'uses. These eples are illustrative and not limiting.

{The term serum" as used in describing the Exam: 1. Polymericlhezamethuleneadipodtamidine dlhydrochlorlde A suspension 01 2.73 parts of diethyl adipodiimidate dihydrochloride (adlponitrile diethyl diiminoether dihydrochloride) CS J OC-(CHs)rC-OC:H:

V laLHcl .HCl

in 3 parts of absolute ethanol is cooled to C.

and mixed with shaking and cooling, with a so-- lution of 1.16 parts of hexamethylcnedianline in 7 parts of absolute ethanol and cooled to 0 C. The mixture is then allowed to stand 48 hours at 25 C. The ethanol is removed by evaporation in vacuo and this residue is then washed with dry ether anddried in vacuo. A white hygroscopic solid results which is soluble in ethanol and in water. The yield is practically quantitative.

This product when tested for bacterial activity by the standard F. D. A. method against Staphylococcus aureus at 37 C. showed a killing dilution of 1 to 20,000 in 10 minutes in the absence of serum. A similar test carried out in the presence of 10% serum showed a killing dilution of 1 to 30,000 in 15 minutes. When tested in the presence of whole blood, this product had a killing dilution of 1 to 1,000 in 30 minutes. The minimum lethal dose of the compound was found to be 45 mg. per kg. when injected subcutaneously in mice.

amidine dlhydrochloride To a suspension of 30.1 parts of sebaconitrile dimethyl diiminoether dihydrochloride in 200 parts of dry methanol cooled to 0 C. is added with shaking 17.2 parts of decamethylenediamine in 25 parts of dry methanol cooled to 0 C. The mixture is then allowed to stand 48 hours at 25C. The methanol is removed by evaporation in vacuo and the residue is washed with dry ether and dried in vacuo. A white hygroscopic solid, which is soluble in methanol, ethanol and in water, results in almost quantitative yield.

This product was tested according to the F. D. A. method against Staphylococcus aureus at 37 C. in water, serum, and whole blood. The resuits are given in the following table.

Table A Killing dilution in parts Organism Medium min. min. min.

Staphylococcus Water l-l0, 00o l-ao, 000 140,000

aurcus.

Do 10% semm. 140, 000 l-al, 000 l-fl), 000 Do lOZflgahole 145,000 l5,000 l5.000

Thus, the linear polymeric amidine salt of this example as prepared above has a good bactericidal potency against Staphylococcus aureus and its ell'ectiveness' against Staphylococcus aureus is not appreciably lowered by the addition of 10% serum to the culture medium.

Polymeric decamethylenes bacodiamidine dihydrochloride was also tested against other organisms. The results are shown in the followin: table. v

Table B Killing dilution in parts Organism Test media 5 min. 10 min. 15 min.

B. cell Water 1-30, 000 l-30, 000 l-30, B. typhom -do l-76, 000 l-l00. 000 l-l00, 000 Streptococcus -do l-50, 000 H00, 000 1-100, 000

moluticua.

Polymeric decamethylenesebacodiamidine dihydrochloride has a high inhibiting action on the growth of bacteria. Tests were made by a standard method for determining bacteriostatlc potency, which consists in adding to broth 9. given amount of the test compound followed by inoculation oi the broth with Staphylococcus aureus organis ns. The growth of the bacteria is then observed for a period of five days. The highest dilution at which no growth takes place is considered as the maximum effective bacteriostatic dilution. Ten cc. of broth containing the polymeric amidine salt in the dilution indicated was inoculated with Staphylococcus aureus. The results, after'maintaining the solution at 37 C. for 2 and 5 days respectively, are indicated in Table C as the dilution necessary to completely inhibit growth. In certain instances 10% blood was added to the broth.

Table C T of Dilution and time Organism g gg of contact Staphylococcus aureus Plain 1,000,000/2 days.

650,000/5 days. D0 10% blood 1,000,000/2 days 500,000/5 days. E. coli Plain 650,000/2 ys. 650,000/5 days. Rtypllosua do 1,000,000/2 days 650,000 5 da s. Streptococcus hemoluticua do 2,600, /2 ays 1,000,000/5 days Do 10% blood 2,600,000/2 days. 2,500,000/5 days.

'The bacteriostatic efiectiveness of the compound of this example against Staphylococcus aureus was also tested by the agar cup plate method which test indicates the penetrating power of the antiseptic agent. The chemical as a dilute water solution is placed in a small depression in agar containing the organism in a plate. The diameter of the area of growth in hibition of the organism is then measured in mil injected intro-peritoneally into mice was 25 mg. perkg. EXAMPLE 3.Polymeric dodecamethylenedodecanodiamz'dine dihydrochloride A suspension of 32.9 parts of dimethyl dodecanodiimidate dihydrochloride (dodecanodinitrile dimethyl dilminoether dihydrochloride) in 200 parts of dry methanol is cooled to 0 C. and mixed with a solution of 20.0 parts of dodecamethylenediamine in 35 parts of methanol cooled to C. The mixture is allowed to stand 48 hours at 25 C. and is then concentrated to dryness in vacuo. The solid product is washed with dry ether and bacteriostatic properties of a group of polymeric amidine salts. These compounds were all prepared according to the methods outline in the previous examples which are further described in in 15 minutes in the absence of serum. In the 40 presence of 10% serum the bactericidal dilution was 1 to 20,000 in 15 minutes. In the presence of whole blood this compound was bactericidal toward Staphylococcus aureus at dilutions of 1 to 5,000 in 30 minutes; This product also showed bacteriostatic activity at dilutions of 1 to 600,000 when tested in broth by the standard method over a period of days at 37 C.

The minimum lethal dose of this compound when injected intraperitoneally in mice was 20 mg. per kg. 1

Examrrr. 4.--Polymeric p-phenylenediethylene I sebacodiamidine 'dihydrochloride A suspension of 30.1 parts of dimethyl sebacodi imidate dihydrochloride (sebaconitrile dimethyl When tested according to the F. D. A. method this product had a very good bactericidal ac-' tivity against Staphylococcus aureus. In the absence of serum in a dilution of 1 to 50,000 killing was eflected in 15 minutes. In the presence of serum the bactericidal dilution was 1 to 20,000 inminutes. The product showed bacteriostatic activity in broth at a dilution of 1 to 40,000 over a time of contact of 5 days.

Table E below summarizes the bactericidal and dried in vacuo. A white, slightly hydroscopic 5 Hunt and Kirby application Serial Number 350,- powder results. This product is obtained in 108. These compounds were all tested by the. quantitative yields and is soluble in water and in standard F. D. A. method for bactericidal activity ethyl alcohol. against Staphylococcus aureus. Their eifective when testedaccording to the F. D. A. method bacteriostatic solution was also determined by against Staphylococcus aureus at 37 0. this prod- 0 the method described in Example -2 which is a uct showed a bactericidal dilution of 1 to 50,000 standard method in bacteriology.

' Table E Bactcrici- Bactericl dlglflgtfiirlgldalmdilliion dali dilliion ilfla'cetive mg [kg u on ac rio- Compound (15 minblood serum who]; static 1: 3? utes) (15 minblood (30 dilution pemm utes) minutes) many Polymeric hexamethylenedodecanodiamidine dihydrochlorlde 1:30, 000 1:20, 000 1:2000 1:25, 000 35 Polymeric p-(phenylenediethylene) dodecanodiam dine dlhydrochloride 1:20, 000 1 10, 000 112000 1:100, 000 15 Pojyl neric hexamethylenesebacodiami- 1:2000 1:5000 1:500 1:250, 000 15 edihydrochlorlde Polymeric dodecam'ethyleneadipodiai midine dihydrochlorlde 1:30, 000 1:20, 000 1:2000 1:500, 000 35 Polglmerio tetramethyleneadlpodiamid e dihydrochloride l:20,000 1 00,000 1:100,000 P01 eric decamethyleneadipodiami- 190,000 1 10,000 1:500 1:l50,000

d edihydrochloride i Polymeric p-(phenylenediethylene)-pphenylcnediacetamidine dihydrochloride 1210000 1:10,000 1:100,000 15 Polymeric decamethyle'nebp-phenylena diacetamidine dlhydroc oride 1 1:10, 000 1 1:20, 000 1:5000 1:400, 000 25 Polymeric xydiphenylenesobecodiemidine d ydrochloride 1:10,000 1:5000 121000 1:500,000 Polymeric p-oxydiphenyleneadipodiamidine dlhydrochloride 1:5, 000 1:500 1:200, 000 Polymeric pamethylenediphenyleneadi podiamid edlhydrochloride 1:10,000 1:10,000 1:00 1:100, 000 Polymeric dioxytriethylenesebacodiamidine dihydrochloride 1110, 000 116000 1:2000 1:20, 000 20 i 10 minutes.

The results in the table show that polymeric linear primary amidine salts in general have bactericidal properties which are diminished only slightly if at all in the presence of blood serum. They maintain a portion of their bactericidal activity even in the presence of whole blood.

The polymeric linear primary amidine salts have been found to be efiective against pathogenic molds. The following example shows-the activity of a compound of this invention toward Trichophyton.

EXAMPLE 5 Polymeric decamethylenesebacodiamidine dihydrochloride when tested by the standard F.

D. A. method showed a killing. dilution for Tripathogenic molds as described in the foregoing example. This fungicidal activity has been demonstrated by means of standard tests utilizing the agar plate method. This consists of dispersing the polymeric linear amidine salts in a nutrient agar favorable to the growth of such fungi as Aspergillus niger (common black mold). The

liquid agar containing the polymeric amidine compound is then poured into sterile Petri plates and when cooled is inoculated with the spores or bits of mycelium of the test fungi. The effective concentration is then determined from a series of test plates containing varying concentration ranges of the. compound and is repre- I mixture of several sented by that concentration completely inhibiting all growth of the fungus mycelium and spore germination upon examination 6 days following the inoculation.

The effectiveness of the polymeric linear amidine salts as mold inhibitors is shown by Table F below in which the figures show the dilution eflective in completely inhibiting the growth of the indicated fungi whentested in The lumber mold indicated in the table is a species of mold which infest cut lumber.

In addition to the marked bactericidal and fungicidal activity the polymeric amidine salts with which this invention is concerned also posses insecticidal activity. For insecticidal purposes the polymeric amidine salts may be applied in any one of the usual methods such as, for example, by spraying solutions or appropriately prepared suspensions thereof in water. They may be used alone or mixed with other insecticidal materials such as rotenone or with inert materials such as talc and clay, or other diluents which would serve to improve their spreading oradherence. A suitable composition for use against insects is illustrated by the following examples which demonstrate the-emciency of this class of compounds as stomach insecticides.

Exsmms 6 A talc dust of the polymeric hexamethyleneadipodiamidine dihydrochloride is prepared by milling appropriately weighed quantities of the polymeric salt with talc. This dust is sprayed onthe foliage of the green bean plant which is then exposed to a known number of Mexican bean beetle larvae. By this spraying treatment 70% of the larvae are destroyed within 5 days with no damage to the foliage.

These polymeric amidine salts are easily incorporated in materials to be protected against insect'attack by simply immersing the goods in an aqueous solution of the compound. They are especially useful on woolen articles and are thus vex desirable as mothprooflng agents. The following example illustrates the mothprooiing activity of these compounds.

Mothprooflng tests were carried out using circular pieces of wool fabric 1%" in diameter. The cloth was soaked in a 2% aqueous solution of the test compound, wrung out and dried and then placed in a small container with ten moth larvae for two weeks. At the end of this time, the number of larvae alive and the percent damage to the cloth was determined. The resuits of these tests are shown on the following table:

Check tests with unimpregnated pieces of fabric showed damage to the goods amounting to to In the foregoing examples the use as pesticides of certain specific linear polymeric amidine salts is described. The invention is not limited to the use of these particular compounds since any linear polymeric amidine salt can be effectively used. The polymeric amidine salts are characterized by the presence of a multiply recurring unit consisting of an amidine salt grouping which is an integral part of the chain and which is linked to organic radicals through carbon. classed as linear polymeric amidine salts are a large variety of compounds. For example, these compounds can be prepared by the reaction of any diiminoether salt which has at least 4 chain atoms between the carbon atoms carrying the nitrogen atoms of the iminoether group, with any organic compound having 2 hydrogen bearing aminonitrogen atoms sepawherein x is the anion of a strong acid, i. e., having an ionization constant of at least 10", preferably a halogen of atomic weight between 35 and 126, and preferably chlorine. R and R. are aliphatic radicals, Y and Y are oxygen or sulfur and the bivalent radical A separating the iminoether groups is any bivalent organic radical free from groups reactive with diamines and free of groups reactive with the diiminoether group. The'bivalent organic radical A may be aliphatic. aromatic, cyclic, or acyclic, homocyclic or heterocyclic. saturated or. unsaturated and may be substituted or tuted with groups which do not react with diamines under the conditions of the polymerization reaction, e. g., they may be ethers, sulfides, ketones.amides, and the like. The preferred iminoether salts are those prepared from aliphatic dinitriles having the formula The compounds useful in this invention in-' acetonitrile, meta-phenylenediacetonitrile, N- (beta-cyanoethyl) -cyanoacetamide, 1,4-dicyanobutane-2, 2,6-dicyanoquinoline, 3,5-dicyanopyridine, beta, beta'-dicyanodiethylether, and beta, beta'-dicyanodiethyl-sulflde.

The iminoether salt may be prepared from such nitriles, hydrogen chloride or bromide and any alcohol. For convenience of preparation a lower alkanol, e. g., methanol, ethanol, isopropanol, or butanol, is usually used as these alcohols are readily available. A mixture of two or more iminoether salts may be employed.

The diamines which may be employed may be formulated as RHNBNHR' in which R and R. are hydrogen or alkyl groups of from one to live carbon atoms, preferably hydrogen. The diamine may contain both a primary and a secondary amino group, for example, N-methylhexamethylenediamine. B ,may be any divalent organic radical having at least 4 atoms in a chain between the two hydrogen-bearing nitrogen atoms and free from groups, other than the two amino groups, reactive with the iminoether groups. B obviously contains no groups reactive with hydrogen-containing amino groups. B, subject to these limitations, may be aliphatic, aromatic, cyclic or acylic, homocyclic or heterocylic, saturated or unsaturated, unsubstituted or substituted with groups which do not react with the diamine or iminoether salt under the conditions of the polymerization reaction. B is preferably clude polymeric amidines having a plurality of groups in the chain and prepared as above described from iminoether salts of polynitriles including trinitriles and the like and polyamines' including alicyclic groups. The polymeric chain may be hydrocarbon with the exception of the recurring amidine salt groups or it may be inhydrocarbon and more preferably a polymethylene group of from six to twenty carbon atoms.

Specific suitable diamines include the following: tetramethylenediamine, pentamethylenediamine, hexamethylenediamine, heptamethylenediamine, octamethylenediamine, nonamethylenediamine, decamethylenediamine, undecamethylene, dodecamethylenediamine, tetradecamethylenediamine, lA-diaminocyclohexane, p-xylylenediamine, p-phenylenediamine, p-bis-(beraaminoethyl) benzene, lA-diaminonaphthalene, p,p-diaminodiphenyl phenylmethane, p,p'-diaminodiphenyl sulfide, p,p'-diaminodiphenyl sulfoxide, p,p'-diaminodiphenyl sulfone, l 4 diaminoanthraquinone, N-methylhexamethylenediamine, N-methyldecamethylenediamine, N,N'-dimethylhexamethylenediamine, MN-dimethyldecamethylenediam-v ine, eAJ-diaminotriphenylmethane, mono-betaalanylethylenediamine, monoglycyltriglycoldiamine i HzNCHzCONHCHzCI-IzOCHzCI-IzOCI-IaCHz-1\TH2,

be employed.

In the preparation of the linear polymeric amidine salts from diimino'ethers and diamines',

amines and monoiminoethers, can be used in ether, p,p'-diaminodii 0 monofunctional reagents, for example, monolimited amounts to control the molecular weight of the polymers by forming end groups on the chain. a

terrupted with groups such as ether, thioether, tertiary amino, carbonamido, sulfone and the like. It may be substituted with halogen, nitro,

hydroxy, mercapto, carboalkoxy, and any other group unreactive in the amidine formation reaction, In the preferred compounds the amidine salt groups in which the'salt is the hydrochloride, for example,

' NHJICI are separated by aliphatic hydrocarbons, preferably polymethylene chains of at least 4 carbon atoms. Compounds of very high bactericidal action are obtained when the length of the hydrocarbon radical separating the amidine groups is from 8 to 12 carbon atoms. The presence of aromatic groups within the hydrocarbon chain of the polymer also yields compounds of good bactericidal action. Although these compounds may exist in a tautomeric form as illustrated by the following formulas:

NEHX Nam o-o-N-c o- =N-C 1i where x is the anion of an acid as previously defined, and these compounds have been described as containing the imino group,

as a lateral substituent in the polymeric chain, it is intended that the claims cover both forms.

In using the polymeric linear amidine salts for the destruction or control of one or more types of pests and organisms that commonly infest plant able adhesives, sticking agents and fixatives andother materials useful in promoting the effectiveness for the particular purpose in mind. Likewise, they may be used in combination with other toxic materials whenever required to obtain maximum effectiveness in the simultaneous control of one or more of several pests. For example, these compounds may be admixed with mercurial germicides, e. g., e-nitro-anhydrohydroxymercuri-ortho-cresol, or the compounds may be used with phenol, the alkyl resorclnols, or the polymeric onium compounds, for example, polymeric quaternary ammonium salts which are al o eflective bactericides.

The pest control compositions herein described are used chiefly in aqueous or alcoholic solutions although they can also be used in organic solvent solutions or as dusts it so desired. They can be used as general purp ise disiniectants such as household disinfectants and as germicides in soaps-cosmetics, antiseptics, mouth washes, kennel sprays, etc. They can also be used iorsterilizing surgical instruments and for rendering animate and inanimate objects, e. g., of leather, glue, or wood, lumber, paper, cellulosic products, etc., germ-free due to their bactericidal action. These compositions have particular value in that they lose relatively little of their bactericidal activity in the presence of blood serumand are even active in the presence or blood. These compounds can be used to great effectiveness against the organisms which afiect the mucous membranes of animals or human beings such as the cocci, and such varied organisms as B. coli, B. tuphosus and the like. They may also be used in the sterilization of sutures, bandages, milk containers, glassware, cans, bottles, and the like.

The above description and examples are intended to be illustrative only. Any modification of or variation therefrom which conforms to the spirit of the invention is intended to be included within the scope of the claims.

What is claimed is:

1. A pest control composition useful for controlling economically harmful lower forms of life, including bacteria, fungi .and insects, containing as an active ingredient a salt of a linear polymeric amidine having as integral chain members recuning bivalent groups consisting of a trivalent nitrogen having one valence attached to a member 01' the class consisting of hydrogen and alkyl groups of from one to five carbon atoms and a amidine having as integral chain members recurring bivalent groups consisting of a trivalent nitrogen having one valence attached to a member of the class consisting of hydrogen and alkyl groups of from one to five carbon atoms and a second valence attached to a chain carbon which is in turn attached by a double bond to a hydrogen-bearing imino group, said recurring amidlne groups being separated by a chain oi at least four linear atoms in organic radicals having their valences stemming from carbon which organic radicals are free from groups reactive with amidine salt groups.

3. A pest control compositionusetul for controlling economically harmiul lower forms of life,

- including bacteria, fungi and insects, containing as an active ingredient a salt of a linear polymeric amidine having as integral chain members recurring bivalent groups consisting of a trivalent nitrogen having one valence attached to a member of the class consisting of hydrogen and alkyl groups of from oneto five carbon atoms and a second valence attached to a chain carbon which is in turn attached by a double bond to a hydrogen-bearing imino group, said recurring amidlne groups being separated by a hydrocarbon chain 0! at least four carbon atoms.

4. A pest control composition useful for controlling economically harmful lower forms 0! life, including bacteria, fungi and insects, containing as an active ingredient a salt of a linear polymeric amidine having as integral chain members recurring bivalent groups consisting of a trivalent nitrogen having one valence attached to a member of the class consisting oi hydrogen and alkyl groups of from one to five carbon atoms and second valence attached to a chain carbon which a second valence attached to a chain carbon which is in turn attached by a double bond to a hydrogen-bearing imino group, said recurring amidine groups being separated by a polymethylene chain or at least four carbon atoms.

' 5. A pest control composition useful for controlling economically harmful lower forms 01 life,

including bacteria, fungi and insects. containing as an active ingredient linear polymeric hexamethyleneadipodiamidine dihydrochloride.

6. A pest control composition useful for controlling economically harmful lower forms of life, including bacteria, fungi and insects, containing as an active ingredient linear polymeric decamethylenesebacodiamidine dihydrochloride.

7. A pest control composition useful for controlling economically harmml lower forms of life, including bacteria, iungi, and insects, containing as an active ingredient linear polymeric decamethyleneadipodiamidine dlhydrochloride.

. JOHN FRANK mm. 

